AS703026 (pimasertib)

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Customer Reviews(1) in vivo invitation

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AS703026 (pimasertib) is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

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Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1008	AZD6244 (Selumetinib)	<1 mg/mL	92 mg/mL	<1 mg/mL
S1036	PD0325901	<1 mg/mL	96 mg/mL	40 mg/mL
S2673	GSK1120212 (JTP-74057)	<1 mg/mL	5 mg/mL	<1 mg/mL
S1102	U0126-EtOH	<1 mg/mL	85 mg/mL	<1 mg/mL
S1177	PD98059	<1 mg/mL	19 mg/mL	<1 mg/mL
S1020	CI-1040 (PD184352)	<1 mg/mL	96 mg/mL	14 mg/mL
S1531	BIX 02189	<1 mg/mL	88 mg/mL	88 mg/mL
S1475	AS703026 (pimasertib)	<1 mg/mL	86 mg/mL	<1 mg/mL
S2617	TAK-733	<1 mg/mL	101 mg/mL	<1 mg/mL
S1530	BIX 02188	<1 mg/mL	43 mg/mL	3 mg/mL
S2134	AZD8330	<1 mg/mL	92 mg/mL	92 mg/mL
S2310	Honokiol	53 mg/mL	53 mg/mL	<1 mg/mL
S1568	PD318088	<1 mg/mL	112 mg/mL	14 mg/mL
S1066	SL327	<1 mg/mL	4 mg/mL	7 mg/mL

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Tech Support & FAQs

Biological Activity

Description	AS703026 is a highly selective and potent non-competitive inhibitor of MEK1/2 with IC50 of 5-11 nM.
Targets	MEK1/2
IC50	5-11 nM ^[1]
In vitro	AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor that binds to the distinctive MEK allosteric site and therefore exhibits exquisite kinase selectivity. AS703026 inhibits growth and survival of human multiple myeloma (MM) cells, including U266 and INA-6, with IC50 of 5 nM and 11 nM, respectively. Such an inhibitory effect by AS703026 is mediated by G0-G1 cell cycle arrest and is accompanied by reduced expresson of the MAF oncogene. AS703026 further induces apoptosis via caspase-3 and PARP cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). ^[1] AS703026 may be an effective therapy in colorectal cancer caused by K-Ras mutation. AS703026 (10 μM) effectively inhibits the ERK pathway, proliferation, and transformation in human DLD-1 colorectal cancer cells what carry a mutant allele of K-Ras (D-MUT). ^[2]
In vivo	AS703026 (15 and 30 mg/kg) significantly inhibits tumor growth in a human plasmacytoma xenograft model of H929 MM cells. This can be correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels. ^[1] AS703026 (10 mg/kg) inhibits tumor growth, and markedly decreases p-ERK level in a xenograft mouse model of human K-Ras mutated (D-MUT) colorectal tumor. ^[2]
Clinical Trials	AS703026 is currently under Phase II clinical trial for acute myeloid leukemia.
Features	AS703026 is a novel, highly selective and potent allosteric inhibitor of MEK1/2.

Protocol(Only for Reference)

Kinase Assay: ^[3]

MEK1 enzyme assays	AS703026 is dissolved in 2.5% DMSO. Activated diphosphorylated MEK (pp-MEK) assays contained 40 μM ³³P-γATP (_AppK_m 8.5 μM), 0.5 nM human-activated MEK1 or MEK2, 1 μM kinase-dead ERK2 (_AppK_m 0.73 μM). All assays are done in buffer containing 20 mM HEPES (pH 7.2), 5 mM 2-mercaptoethanol, 0.15 mg/mL BSA, and 10 mM MgCl₂. The final concentration of ³³P- ATP is 0.02 μCi/μL for all the assays. pp-MEK kinase reactions are stopped after 40 min by transferring 30 μL of reaction mixture to Durapore 0.45-μm filters plates containing 12.5% TCA. Filters are dried and read with liquid scintilant on a TopCount. Concentration response data are analyzed for IC50. 0.2 nM recombinant human MEK1 or MEK2 is preincubated with vehicle or with AS703026 for 40 minutes in reaction buffer to determine IC50 of initially unphosphorylated MEK (u-MEK). Phosphorylation/activation is initiated by the addition of a final concentration of 20 nM final B-Raf^V600E and 30 μM final ATP for 10 min. B-Raf activity is then quenched by addition of the B-Raf inhibitor SB590885 (final concentration 100 nM), and MEK kinase activity is assayed by the addition of 1 μM KD-ERK2 and 0.02 μCi/μL ³³P-ATP in reaction buffer. The kinase reactions are stopped after 90 min by transferring 30μL of reaction mixture to a Durapore filter plate, and read as above.

MEK1 enzyme assays

AS703026 is dissolved in 2.5% DMSO. Activated diphosphorylated MEK (pp-MEK) assays contained 40 μM ³³P-γATP (_AppK_m 8.5 μM), 0.5 nM human-activated MEK1 or MEK2, 1 μM kinase-dead ERK2 (_AppK_m 0.73 μM). All assays are done in buffer containing 20 mM HEPES (pH 7.2), 5 mM 2-mercaptoethanol, 0.15 mg/mL BSA, and 10 mM MgCl₂. The final concentration of ³³P- ATP is 0.02 μCi/μL for all the assays. pp-MEK kinase reactions are stopped after 40 min by transferring 30 μL of reaction mixture to Durapore 0.45-μm filters plates containing 12.5% TCA. Filters are dried and read with liquid scintilant on a TopCount. Concentration response data are analyzed for IC50. 0.2 nM recombinant human MEK1 or MEK2 is preincubated with vehicle or with AS703026 for 40 minutes in reaction buffer to determine IC50 of initially unphosphorylated MEK (u-MEK). Phosphorylation/activation is initiated by the addition of a final concentration of 20 nM final B-Raf^V600E and 30 μM final ATP for 10 min. B-Raf activity is then quenched by addition of the B-Raf inhibitor SB590885 (final concentration 100 nM), and MEK kinase activity is assayed by the addition of 1 μM KD-ERK2 and 0.02 μCi/μL ³³P-ATP in reaction buffer. The kinase reactions are stopped after 90 min by transferring 30μL of reaction mixture to a Durapore filter plate, and read as above.

Cell Assay: ^[1]

Cell lines	U266 and INA-6 cells
Concentrations	2 nM - 20 μM (stock: 10 mM in DMSO)
Incubation Time	48 hours
Method	Cytotoxicity assays for AS703026 are assessed by measuring both [³H]thymidine incorporation and MTT dye absorbance. Cells (1 × 10⁴ per well) are cultured in 96-well plates for 3 days. For the [³H]thymidine incorporation assay, cells are pulsed with 18.5 kBq/well [³H]thymidine for 6 hours, harvested onto glass fibre filters, and counted in a β-scintillation counter. Cell cycle analysis is assessed by propidium iodide (PI) staining using flow cytometry. AS703026-induced apoptosis is determined by annexin-V/PI staining and flow cytometric data analysis.

Animal Study: ^[1]

Animal Models	H929 MM xenografts are established in CB17 (SCID) mice
Formulation	10 mg/mL, dissolved in 0.5% carboxymethylcellulose / 0.25% Tween20
Dosages	15 or 30 mg/kg
Administration	Oral gavage twice daily

1

References

Chemical Information

Download AS703026 (pimasertib) SDF

Molecular Weight (MW)	431.20
Formula	C₁₅H₁₅FIN₃O₃
CAS No.	1236699-92-5, 1236361-78-6 (HCl)
Synonyms	MSC1936369B

Solubility (25°C) DMSO 86 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	(S)-N-(2,3-dihydroxypropyl)-3-(2-fluoro-4-iodophenylamino)isonicotinamide

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Research Area

Customer Reviews (1)

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Rating

Source

Dr. Zhang of Tianjin Medical University. AS703026 (pimasertib) purchased from Selleck

Method

Western blot

Cell Lines

A549 cells

Concentrations

0-10 μM

Incubation Time

3 h

Results

AS703026 decreased protein expression levels of ERK1/2, but had no effect on ERK1/2 phosphorylation.

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3Monday–Friday 9:00 AM–5:00 PM (Central Time)

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AZD6244 (Selumetinib, ARRY-142886) is highly potent to inhibit MEK1 with IC50 of 14 nM.
CI-1040 (PD184352)

CI-1040 (PD 184352) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM.
PD0325901

PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM.
SL327
SL327 is a selective inhibitor for MEK1 and MEK2 with IC50 of 0.18 μM and 0.22 μM, respectively.
U0126-EtOH

U0126-EtOH is a highly selective inhibitor of MEK1 and MEK2 with IC50 of 0.07 μM and 0.06 μM, respectively.
PD98059

PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM.
BIX 02188
BIX02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM.
BIX 02189

BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM.
PD318088

PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor.
AZD8330

AZD8330 (ARRY-424704) is a MEK 1/2 inhibitor with IC50 of 7 nM.

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Validation & Quality Control

Customer Reviews(1) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

AS703026 (pimasertib) is available in the following compound libraries:

Product Information

Compare MEK Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[3]

Cell Assay: ^[1]

Animal Study: ^[1]

References

Chemical Information

Research Area

Customer Reviews (1)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

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S1036	PD0325901	<1 mg/mL	96 mg/mL	40 mg/mL
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S1531	BIX 02189	<1 mg/mL	88 mg/mL	88 mg/mL
S1475	AS703026 (pimasertib)	<1 mg/mL	86 mg/mL	<1 mg/mL
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S1568	PD318088	<1 mg/mL	112 mg/mL	14 mg/mL
S1066	SL327	<1 mg/mL	4 mg/mL	7 mg/mL

Choose Your Country or Region

Product Categories

AS703026 (pimasertib)

Validation & Quality Control

Customer Reviews(1) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

AS703026 (pimasertib) is available in the following compound libraries:

Product Information

Compare MEK Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [3]

Cell Assay: [1]

Animal Study: [1]

References

Chemical Information

Research Area

Customer Reviews (1)

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related MEK Inhibitors

MAPK Pathway Products

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Kinase Assay: ^[3]

Cell Assay: ^[1]

Animal Study: ^[1]